Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1

• Type: Article in International Scientific Journal
• Date: 2011

Authors

ferreira, m (Author) Other; torraco, a (Author) Other; rizza, t (Author) Other; fattori, f (Author) Other; meschini, mc (Author) Other; castana, c (Author) Other; go, ne (Author) Other; nargang, fe (Author) Other; duarte, m (Author) ICBAS; piemonte, f (Author) Other; dionisi-vici, c (Author) Other; videira, a (Author) FEUP; vilarinho, l (Author) Other; santorelli, fm (Author) Other; carrozzo, r (Author) Other; bertini, e (Author) Other

Journal

Title: Neurogenetics

Vol. 12

Pages: 9-17

ISSN: 1364-6745

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-002-VCW

DOI: 10.1007/s10048-010-0265-2

Abstract (EN): We present clinical, neuroimaging, and molecular data on the identification of a new homozygous c.1783A > G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy, a clinical and neuroradiological entity originally related to unknown defects of the mitochondrial energy metabolism. In both sibs, the muscle biopsy showed severe reduction of complex I enzyme activity, which was not obvious in fibroblasts. We also observed complex I dysfunction in a Neurospora crassa model of the disease, obtained by insertional mutagenesis, and in patient fibroblasts grown in galactose. Altogether, these results indicate that the NDUFS1 mutation is responsible for the disease and complex I deficiency. Clinical presentation of complex I defect is heterogeneous and includes an ample array of clinical phenotypes. Expanding the number of allelic variants in NDUFS1, our findings also contribute to a better understanding on the function of complex I.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9